Wafer-Scale Synthesis of Highly Oriented 2D Topological Semimetal PtTe2 via Tellurization.

Platinum ditelluride (1T-PtTe2) is a two-dimensional (2D) topological semimetal with a distinctive band structure and flexibility of van der Waals integration as a promising candidate for future electronics and spintronics. Although the synthesis of large-scale, uniform, and highly crystalline films of 2D semimetals system is a prerequisite for device application, the synthetic methods meeting these criteria are still lacking. Here, we introduce an approach to synthesize highly oriented 2D topological semimetal PtTe2 using a thermally assisted conversion called tellurization, which is a cost-efficient method compared to the other epitaxial deposition methods. We demonstrate that achieving highly crystalline 1T-PtTe2 using tellurization is not dependent on epitaxy but rather relies on two critical factors: (i) the crystallinity of the predeposited platinum (Pt) film and (ii) the surface coverage ratio of the Pt film considering lateral lattice expansion during transformation. By optimizing the surface coverage ratio of the epitaxial Pt film, we successfully obtained 2 in. wafer-scale uniformity without in-plane misalignment between antiparallelly oriented domains. The electronic band structure of 2D topological PtTe2 is clearly resolved in momentum space, and we observed an interesting 6-fold gapped Dirac cone at the Fermi surface. Furthermore, ultrahigh electrical conductivity down to ∼3.8 nm, which is consistent with that of single crystal PtTe2, was observed, proving its ultralow defect density.

Layer-Controlled Growth of Single-Crystalline 2D Bi2O2Se Film Driven by Interfacial Reconstruction.

As semiconductor scaling continues to reach sub-nanometer levels, two-dimensional (2D) semiconductors are emerging as a promising candidate for the post-silicon material. Among these alternatives, Bi2O2Se has risen as an exceptionally promising 2D semiconductor thanks to its excellent electrical properties, attributed to its appropriate bandgap and small effective mass. However, unlike other 2D materials, growth of large-scale Bi2O2Se films with precise layer control is still challenging due to its large surface energy caused by relatively strong interlayer electrostatic interactions. Here, we present the successful growth of a wafer-scale (∼3 cm) Bi2O2Se film with precise thickness control down to the monolayer level on TiO2-terminated SrTiO3 using metal-organic chemical vapor deposition (MOCVD). Scanning transmission electron microscopy (STEM) analysis confirmed the formation of a [BiTiO4]1- interfacial structure, and density functional theory (DFT) calculations revealed that the formation of [BiTiO4]1- significantly reduced the interfacial energy between Bi2O2Se and SrTiO3, thereby promoting 2D growth. Additionally, spectral responsivity measurements of two-terminal devices confirmed a bandgap increase of up to 1.9 eV in monolayer Bi2O2Se, which is consistent with our DFT calculations. Finally, we demonstrated high-performance Bi2O2Se field-effect transistor (FET) arrays, exhibiting an excellent average electron mobility of 56.29 cm2/(V·s). This process is anticipated to enable wafer-scale applications of 2D Bi2O2Se and facilitate exploration of intriguing physical phenomena in confined 2D systems.

Large Memory Window of van der Waals Heterostructure Devices Based on MOCVD-Grown 2D Layered Ge4 Se9.

Van der Waals (vdW) heterostructures have drawn much interest over the last decade owing to their absence of dangling bonds and their intriguing low-dimensional properties. The emergence of 2D materials has enabled the achievement of significant progress in both the discovery of physical phenomena and the realization of superior devices. In this work, the group IV metal chalcogenide 2D-layered Ge4 Se9 is introduced as a new selection of insulating vdW material. 2D-layered Ge4 Se9 is synthesized with a rectangular shape using the metalcorganic chemical vapor deposition system using a liquid germanium precursor at 240 °C. By stacking the Ge4 Se9 and MoS2 , vdW heterostructure devices are fabricated with a giant memory window of 129 V by sweeping back gate range of ±80 V. The gate-independent decay time reveals that the large hysteresis is induced by the interfacial charge transfer, which originates from the low band offset. Moreover, repeatable conductance changes are observed over the 2250 pulses with low non-linearity values of 0.26 and 0.95 for potentiation and depression curves, respectively. The energy consumption of the MoS2 /Ge4 Se9 device is about 15 fJ for operating energy and the learning accuracy of image classification reaches 88.3%, which further proves the great potential of artificial synapses.

Yeast polyubiquitin unit regulates synaptonemal complex formation and recombination during meiosis.

Ubiquitin is highly conserved in most eukaryotes and involved in diverse physiological processes, including cell division, protein quality control, and protein degradation mediated by the ubiquitin-proteasome system after heat shock, glucose-starvation, and oxidative stress. However, the role of the ubiquitin gene UBI4, which contains five consecutive head-to-tail ubiquitin repeats, in meiosis has not been investigated. In this study, we show that the Saccharomyces cerevisiae polyubiquitin precursor gene, UBI4, is required to promote synaptonemal complex (SC) formation and suppress excess double-strand break formation. Moreover, the proportion of Zip1 polycomplexes, which indicate abnormal SC formation, in cells with a mutation in UBI4 (i.e., ubi4Δ cells) is higher than that of wild-type cells, implying that the UBI4 plays an important role in the early meiotic prophase I. Interestingly, although ubi4Δ cells rarely form full-length SCs in the pachytene stage of prophase I, the Zip3 foci are still seen, as in wild-type cells. Moreover, ubi4Δ cells proficiently form crossover and noncrossover products with a slight delay compared to wild-type cells, suggesting that UBI4 is dispensable in SC-coupled recombination. Our findings demonstrate that UBI4 exhibits dual functions that are associated with both positive and negative roles in SC formation and recombination during meiosis.

The Cumulative Effect of Antipsychotic Usage on Mortality in Schizophrenia: A Nationwide Population-based Cohort Study in Korea.

Objective: To investigate the cumulative effect of antipsychotics at different dosages on mortality in patients with schizophrenia. Methods: We analyzed data from the Korean National Health Insurance System-National Sample Cohort covering the 2002-2013 period. We used Cox regression analysis to calculate hazard ratios for mortality risks according to cumulative antipsychotic exposure levels (low, moderate, and high). Results: Our analyses revealed no significant association between antipsychotic exposure and mortality (either all-cause or cause-specific) in patients with schizophrenia. Conclusion: Our results imply that the excess mortality of patients with schizophrenia is attributable to factors other than antipsychotic usage.

Self-Injurious Behavior Rate in the Short-Term Period of the COVID-19 Pandemic in Korea.

BACKGROUND: The objective of this study was to investigate the trend of self-injurious behavior (SIB) among persons who were directly impacted by coronavirus disease 2019 (COVID-19), especially those with pre-existing mental disorders. METHODS: Using the National Health Insurance Service-COVID-19 database cohort, the monthly SIB rate was calculated by COVID-19 subgroups (i.e., positive for COVID-19 test, negative for COVID-19 test, and non-COVID-19 test [control]). In addition, moderated regression analysis was utilized to examine the statistical difference of SIB (suicide attempt and non-suicidal self-injury using ICD-10 code) trend between COVID-19 subgroups and with and without pre-existing mental disorder. RESULTS: A total of 328,373 persons were included in the cohort study. Of these, 212,678 had been tested for COVID-19, and 7,713 of them were confirmed positive. During the pandemic peak, the "negative for COVID-19" group showed a large increase (P = 0.003) in SIB rates compared to the control group, the "positive for COVID-19" group showed a decreasing trend, but not significant (P = 0.314). Among those who were tested for COVID-19, those with pre-existing mental disorders showed an increasing trend of SIB compared to those without pre-existing mental disorders, however statistically insignificant (P = 0.137). CONCLUSION: Our results suggest that people who are tested for COVID-19 are at a high risk of SIB during the peak COVID-19 pandemic. Therefore, screening for suicide risk and psychological interventions is needed for these high-risk groups.

The Trend of Psychiatric Visits and Psychiatric Medication Prescription Among People Tested for SARS-CoV-2 During the Initial Phase of COVID-19 Pandemic in South Korea.

OBJECTIVE: The objective of this study was to monitor the trend of psychiatric visits and medication prescriptions among people tested for SARS-CoV-2 during the initial phase of coronavirus disease 2019 (COVID-19) pandemic in South Korea. METHODS: We conducted a population-based cohort study using data from the National Health Insurance Service (NHIS) linked to the Korea Disease Control and Prevention Agency (KDCA) data. The overall trend of psychiatric visits during COVID-19 for each month was compared to the month prior to COVID-19. The number of psychiatric medication prescription records was monitored from January 2019 to May 2020. RESULTS: A total of 212,678 individuals were tested for SARS-CoV-2 between January 2020 and May 2020. Among these individuals, 72.1% (n=153,309) did not have pre-existing mental illness, and 27.9% (n=59,369) had pre-existing mental illness. We found that most psychiatric visits were made in March, and patients without pre-existing mental illness significantly increased in psychiatric outpatients during the COVID-19 pandemic (p trend<0.001). In addition, psychiatric medication prescriptions were the most prescribed between March and April 2020. CONCLUSION: We identified a rising trend in psychiatric visits and medication prescriptions among people who were tested for SARSCoV-2 during the initial phase of COVID-19 pandemic in South Korea.

Diffusion-Controlled Crystallization of Calcium Phosphate in a Hydrogel toward a Homogeneous Octacalcium Phosphate/Agarose Composite.

Diffusion-controlled crystallization in a hydrogel has been investigated to synthesize organic/inorganic hybrid composites and obtain a fundamental understanding of the detailed mechanism of biomineralization. Although calcium phosphate/hydrogel composites have been intensively studied and developed for the application of bone substitutes, the synthesis of homogeneous and integrated composites remains challenging. In this work, diffusion-controlled systems were optimized by manipulating the calcium ion flux at the interface, concentration gradient, and diffusion coefficient to synthesize homogeneous octacalcium phosphate/hydrogel composites with respect to the crystal morphology and density. The ion flux and local pH play an important role in determining the morphology, density, and phase of the crystals. This study suggests a model system that can reveal the relation between local conditions and the resulting crystal phase in diffusion-limited systems and provides a synthetic method for homogeneously organized organic/inorganic composites.

Identification and evaluation of midbrain specific longevity-related genes in exceptionally long-lived but healthy mice.

Brain aging is a complex biological process that is affected by both genetic background and environment. The transcriptomic analysis of aged human and rodent brains has been applied to identify age-associated molecular and cellular processes for which intervention could possibly restore declining brain functions induced by aging. However, whether these age-associated genetic alterations are indeed involved in the healthy aging of the brain remains unclear. We herein characterized a naturally occurring, extremely long-lived (34 months of age) but healthy mouse group retaining well-preserved motor functions. Strikingly, these long-lived mice maintained tyrosine hydroxylase expression and dopaminergic fiber densities, even in the presence of persistent neuroinflammation and expression of aging markers. Combined with Endeavor gene prioritization, we identified the following midbrain-specific longevity-associated genes in the midbrain of these mice: aimp2, hexb, cacybp, akt2, nrf1, axin1, wwp2, sp2, dnajb9, notch, traf7, and lrp1. A detailed biochemical analysis of the midbrain of these long-lived mice confirmed the increased expression of Nrf1 and the activation of Akt1 and 2. Interestingly, dopaminergic neuroprotective and age-associated E3 ubiquitin ligase parkin expression was retained at high levels in the aforementioned midbrains, possibly supporting the suppression of its toxic substrates AIMP2 and PARIS. In contrast, the 24-month-old mice with dopaminergic neurite deficits failed to maintain parkin expression in the midbrain. AIMP2-induced cytotoxicity, mitochondrial stress, and neurite toxicity can be prevented by overexpression of parkin, Akt1, and Nrf1 in SH-SY5Y and PC12 cells, and basal expression of parkin, Akt1, and Nrf1 is required for maintenance of mitochondrial function and neurite integrity in PC12 cells. Taken together, this longevity-associated pathway could be a potential target of intervention to maintain nigrostriatal dopaminergic fibers and motor ability to ensure healthy longevity.

Enhancement of Photoresponse on Narrow-Bandgap Mott Insulator α-RuCl3 via Intercalation.

Charge doping to Mott insulators is critical to realize high-temperature superconductivity, quantum spin liquid state, and Majorana fermion, which would contribute to quantum computation. Mott insulators also have a great potential for optoelectronic applications; however, they showed insufficient photoresponse in previous reports. To enhance the photoresponse of Mott insulators, charge doping is a promising strategy since it leads to effective modification of electronic structure near the Fermi level. Intercalation, which is the ion insertion into the van der Waals gap of layered materials, is an effective charge-doping method without defect generation. Herein, we showed significant enhancement of optoelectronic properties of a layered Mott insulator, α-RuCl3, through electron doping by organic cation intercalation. The electron-doping results in substantial electronic structure change, leading to the bandgap shrinkage from 1.2 eV to 0.7 eV. Due to localized excessive electrons in RuCl3, distinct density of states is generated in the valence band, leading to the optical absorption change rather than metallic transition even in substantial doping concentration. The stable near-infrared photodetector using electronic modulated RuCl3 showed 50 times higher photoresponsivity and 3 times faster response time compared to those of pristine RuCl3, which contributes to overcoming the disadvantage of a Mott insulator as a promising optoelectronic device and expanding the material libraries.

Analyzing Untreated Alcohol Use Disorder and Factors Related to Help-Seeking Status.

OBJECTIVE: Alcohol use disorder (AUD) is a global burden but is also one of the most undertreated mental disorders. This study estimates the treatment rate (i.e., help-seeking status) of high-risk drinkers and factors associated with not receiving treatment in Korea using nationally representative National Health Insurance Service-National Sample Cohort (NHIS-NSC) data. METHODS: Among 1,025,340 participants, we eliminated those under 20 and those who did not respond to the question regarding alcohol consumption. High-risk drinkers were classified based on their frequency and quantity of alcohol consumption (4 or more drinks for women, 5 or more drinks for men per day on average). In total, 32,225 high-risk drinkers were checked for an actual AUD diagnosis to see their treatment-seeking status. RESULTS: Among 32,225 high-risk drinkers, only 1.24% had an AUD diagnosis, showing that over 98% of those who could be diagnosed with AUD are not seeking treatment. Factors associated with not seeking treatment were female sex, BMI higher or equal to 18.6, former smoker, middle-aged, and Charlson Comorbidity Index (CCI). CONCLUSION: Our data show that many high-risk drinkers do not seek treatment in Korea. Experts, policymakers, and clinicians should promote help-seeking behavior for AUD and pay close attention to those at risk of not receiving treatment for AUD.

Electric-Field-Induced Reversible Phase Transitions in a Spontaneously Ion-Intercalated 2D Metal Oxide.

Electric field driven reversible phase transitions in two-dimensional (2D) materials are appealing for their potential in switching applications. Here, we introduce potassium intercalated MnO2 as an exemplary case. We demonstrate the synthesis of large-area single-crystal layered MnO2 via chemical vapor deposition as thin as 5 nm. These crystals are spontaneously intercalated by potassium ions during the synthesis. We showed that the charge transport in 2D K-MnO2 is dominated by motion of hydrated potassium ions in the interlayer space. Under a few volts bias, separation of potassium and the structural water leads to formation of different phases at the opposite terminals, and at larger biases K-MnO2 crystals exhibit reversible layered-to-spinel phase transition. These phase transitions are accompanied by electrical and optical changes in the material. We used the electric field driven ionic motion in K-MnO2 based devices to demonstrate the memristive capabilities of two terminal devices.

Growth and Interlayer Engineering of 2D Layered Semiconductors for Future Electronics.

Layered materials that do not form a covalent bond in a vertical direction can be prepared in a few atoms to one atom thickness without dangling bonds. This distinctive characteristic of limiting thickness around the sub-nanometer level allowed scientists to explore various physical phenomena in the quantum realm. In addition to the contribution to fundamental science, various applications were proposed. Representatively, they were suggested as a promising material for future electronics. This is because (i) the dangling-bond-free nature inhibits surface scattering, thus carrier mobility can be maintained at sub-nanometer range; (ii) the ultrathin nature allows the short-channel effect to be overcome. In order to establish fundamental discoveries and utilize them in practical applications, appropriate preparation methods are required. On the other hand, adjusting properties to fit the desired application properly is another critical issue. Hence, in this review, we first describe the preparation method of layered materials. Proper growth techniques for target applications and the growth of emerging materials at the beginning stage will be extensively discussed. In addition, we suggest interlayer engineering via intercalation as a method for the development of artificial crystal. Since infinite combinations of the host-intercalant combination are possible, it is expected to expand the material system from the current compound system. Finally, inevitable factors that layered materials must face to be used as electronic applications will be introduced with possible solutions. Emerging electronic devices realized by layered materials are also discussed.

Joint effect of depression and health behaviors or conditions on incident cardiovascular diseases: A Korean population-based cohort study.

BACKGROUND: The precise relationships among depression, risk factors for cardiovascular disease (CVD), and incident CVD remain uncertain. This study examined the joint effect of depression and other CVD risk factors on the incidence of CVD. METHODS: We conducted a prospective cohort study using South Korea's National Health Insurance Service-National Sample Cohort (NHIS-NSC). To estimate incident CVD, 199,544 participants without CVD diagnosed with depression between 2003 and 2005 were followed through 2013. The clinician's diagnosis used measurements for depression, CVD risk factors, and CVD. RESULTS: Controlling for other CVD risk factors, depressed individuals had a higher risk for ischemic heart disease (AHR, 1.01; 99%%CI, 1.01-1.50) and other forms of heart disease likely related to atherosclerosis (AHR, 1.43; 99%%CI, 1.13-1.82). There were no statistically significant interactions between depression and CVD risk factors. However, when depression was comorbid with overweight or diabetes, there was a higher risk for incident ischemic heart disease, as compared to depression or CVD risk factors alone. For other forms of heart disease likely related to atherosclerosis, the coexistence of depression and physical inactivity or overweight showed a similar pattern to that shown in ischemic heart disease. LIMITATIONS: The severity of depression was not reported for depressed patients, and our dataset provided a limited number of covariates. Also, the self-reported health behavior data may be biased. CONCLUSION: As depression could be a significant predictor of incident CVD independently with other CVD risk factors, professionals should recognize and manage depression as a major CVD risk factor.

Illuminating the treatment gap of mental disorders: A comparison of community survey-based and national registry-based prevalence rates in Korea.

Estimating the prevalence rates of mental disorders is important for developing prevention, treatment, and research plans. Given that survey-based and registry-based prevalence rates of mental disorders each have pros and cons yet complement one another, it is important to consider both assessments when investigating the prevalence rates of mental disorders. However, no study has utilized actual treatment data of patients with mental disorders when investigating the treatment gap. The results of the Survey of Mental Disorders in Korea from 2006, 2011, and 2016 and data from the National Health Insurance Database were used to compare survey-based and registry-based prevalence rates for 17 disorders, as well the prevalence rates for each sex. The survey-based prevalence rate was higher for 10 years in Korea. However, the registry-based prevalence rate continuously increased. By 2016 the two rates were comparable. For alcohol use and nicotine use disorders, the survey-based prevalence rate was consistently higher than the registry-based prevalence rate, while the registry-based prevalence rate was higher for schizophrenia. Mood disorder rates were similar between the two types. Most anxiety disorders had a higher survey-based prevalence rate, except for panic disorder. Men had a higher survey-based prevalence rate, whereas women had a higher registry-based prevalence rate of mental disorders. Korea's registry-based prevalence rate of mental disorders has consistently increased due to various efforts in the field. However, there is still room for improvement, especially in mental health literacy. Therefore, each disorder and patient sex needs to be considered separately when planning education and campaigns.

The cost-of-illness trend of schizophrenia in South Korea from 2006 to 2016.

Globally, about one in four people develop a psychiatric disorder during their lifetime. Specifically, the lifetime prevalence of schizophrenia is about 0.48%, and schizophrenia can have detrimental effects on a patient's life. Therefore, estimating the economic burden of schizophrenia is important. We investigated the cost-of-illness trend of schizophrenia in South Korea from 2006 to 2016. The cost-of-illness trend was estimated from a societal perspective using a prevalence-based approach for direct costs and a human capital approach for indirect costs. We utilized information from the following sources: 1) National Health Insurance Service, 2) Korean Statistical Information Service, Statistics Korea, 3) the National Survey of Persons with Disabilities, 4) Budget and Fund Operation Plan, Ministry of Justice, 5) Budget and Fund Operation Plan, Ministry of Health and Welfare, and 6) annual reports from the National Mental Health Welfare Commission. Direct healthcare costs, direct non-healthcare costs, and indirect costs by sex and age group were calculated along with sensitivity analyses of the estimates. The cost-of-illness of schizophrenia in Korea steadily increased from 2006 to 2016, with most costs being indirect costs. Individuals in their 40s and 50s accounted for most of the direct and indirect costs. Among indirect costs, the costs due to unemployment were most prevalent. Our estimation implies that schizophrenia is associated with a vast cost-of-illness in Korea. Policymakers, researchers, and physicians need to put effort into shortening the duration of untreated psychosis, guide patients to receive community-care-based services rather than hospital-based services and empower lay people to learn about schizophrenia.

Lactobacillus paracasei-derived extracellular vesicles attenuate the intestinal inflammatory response by augmenting the endoplasmic reticulum stress pathway.

Lactobacillus paracasei is a major probiotic and is well known for its anti-inflammatory properties. Thus, we investigated the effects of L. paracasei-derived extracellular vesicles (LpEVs) on LPS-induced inflammation in HT29 human colorectal cancer cells and dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice. ER stress inhibitors (salubrinal or 4-PBA) or CHOP siRNA were utilized to investigate the relationship between LpEV-induced endoplasmic reticulum (ER) stress and the inhibitory effect of LpEVs against LPS-induced inflammation. DSS (2%) was administered to male C57BL/6 mice to induce inflammatory bowel disease, and disease activity was measured by determining colon length, disease activity index, and survival ratio. In in vitro experiments, LpEVs reduced the expression of the LPS-induced pro-inflammatory cytokines IL-1α, IL-1ß, IL-2, and TNFα and increased the expression of the anti-inflammatory cytokines IL-10 and TGFß. LpEVs reduced LPS-induced inflammation in HT29 cells and decreased the activation of inflammation-associated proteins, such as COX-2, iNOS and NFκB, as well as nitric oxide. In in vivo mouse experiments, the oral administration of LpEVs also protected against DSS-induced colitis by reducing weight loss, maintaining colon length, and decreasing the disease activity index (DAI). In addition, LpEVs induced the expression of endoplasmic reticulum (ER) stress-associated proteins, while the inhibition of these proteins blocked the anti-inflammatory effects of LpEVs in LPS-treated HT29 cells, restoring the pro-inflammatory effects of LPS. This study found that LpEVs attenuate LPS-induced inflammation in the intestine through ER stress activation. Our results suggest that LpEVs have a significant effect in maintaining colorectal homeostasis in inflammation-mediated pathogenesis.

Assessment of clinical performance of an ultrasensitive nanowire assay for detecting human papillomavirus DNA in urine.

OBJECTIVE: To evaluate whether HPV DNA in urine has potential advantages as an alternative biomarker for HPV-based cervical cancer screening. METHODS: Among patients with Cobas HPV test results, a total of 67 HPV-positive (n = 42) and -negative (n = 25) women who agreed to participate in this study were willing to provide paired cervical and urine samples, and we observed concordance between sample types from each patient in identifying HPV genotypes using the nanowire assay. RESULTS: We detected high-risk strains of HPV DNA in unprocessed urine specimens using polyethyleneimine-conjugated nanowires (PEI-NWs). Concordance for high-risk HPV (hrHPV) between paired urine and cervical samples was 90.4% (κ = 0.90; 95% CI: 0.80-100.00). The virological sensitivity and specificity for detection of HPV DNA from a small urine sample (200 µL) were 81.3% (κ = 0.83; 95% CI: 62.1-100.0) and 98.0% (κ = 0.83; 95% CI: 94.2-100.0) for HPV16 group, 100.0% (κ = 0.65; 95% CI: 100.0-100.0) and 95.3% (κ = 0.65; 95% CI: 90.1-100.0) for HPV18 group, and 96.4% (κ = 0.97; 95% CI: 89.6-100.0) and 100.0% (κ = 0.97; 95% CI: 100.0-100.0) for other hrHPV group, respectively. CONCLUSIONS: The nanowire assay demonstrated excellent ability to identify HPV DNA from urine specimens. We observed an excellent agreement in the detection of high-risk HPV between paired urine and cervical samples, even with small urine sample volume.

Comorbidity of Alcohol Use and Other Psychiatric Disorders and Suicide Mortality: Data from the South Korean National Health Insurance Cohort, 2002 to 2013.

BACKGROUND: Previous studies have indicated that alcohol use disorder (AUD) and other psychiatric disorders increase the risk of suicide mortality. However, little research has investigated the concomitant effect of comorbid psychiatric disorders on suicide mortality. This study aimed to investigate the effect of comorbid AUD on suicide mortality of individuals with another psychiatric disorder using a national data sample. METHODS: We used the National Health Insurance Service-National Sample Cohort data from 2002 to 2013. We selected individuals with specific psychiatric disorders based on the International Classification of Diseases, 10th revision (F10-F48). Overall, the study included 741,601 participants. We utilized a prioritization process to identify the primary diagnosis for those with multiple diagnoses. All-cause mortality rates and suicide rates per 100,000 person-year (days) and the standardized mortality ratio (SMR) were calculated. Then, we compared the suicide-specific SMR of 3 different groups: (i) specific psychiatric disorder versus general public; (ii) specific psychiatric disorder comorbid with AUD versus general public; and (iii) specific psychiatric disorder comorbid with AUD versus specific psychiatric disorder without comorbid AUD. RESULTS: Patients with any specific psychiatric disorder showed higher suicide-specific SMR compared to the general population. Being comorbid with AUD further increased the risk of suicide among psychiatric patients. In particular, patients with bipolar affective disorders, organic mental disorders, or depressive disorders comorbid with AUD had about 2 to 4 times higher suicide-specific SMR compared to those without AUD (bipolar affective disorder: SMR = 3.01, 95% confidence interval (CI) [1.49, 4.54]; organic mental disorder: SMR = 3.43, 95% CI [1.05, 5.81]; depressive disorder: SMR = 2.06, 95% CI [1.52, 2.61]). CONCLUSIONS: Our data indicate that having a psychiatric disorder increases the risk of committing suicide. More importantly, comorbid AUD further increases this risk of suicidal death for certain psychiatric disorders. This shows the importance of determining whether patients with psychiatric disorders have comorbid AUD to prevent suicide.

Anti-TNF effect of combined pravastatin and cilostazol treatment in an in vivo mouse model.

Objectives: Pravastatin and cilostazol are used as lipid-lowering and antiplatelet agents, respectively. Regarding their well-known anti-inflammatory effects, the additive effect of the two drugs on anti-TNF functions has not yet been investigated. In the present investigation, the beneficial effect of combined pravastatin and cilostazol on their anti-TNF activities was assessed using an in vivo mouse model. Methods: Mice were pretreated with pravastatin and/or cilostazol (40 mg/kg of each), orally once two hour prior to an LPS (5 mg/kg, i.p.) challenge. One hour post challenge, blood and descending aorta were collected for serum TNF levels and immune cell infiltration analyses. For survival analysis, pravastatin and/or cilostazol (40 mg/kg of each) were administered 30 minutes prior to d-galactosamine administration (700 mg/kg, i.p.) and TNF (10 µg/kg, i.p.) challenge and mice survival was monitored. We also examined the effect of either drug or the combination of drugs on TNF-mediated MAPK and NF-κB signaling, using Western blot analysis. Results: Combined treatment of pravastatin and cilostazol significantly decreased serum TNF release and immune cell infiltration in the descending aorta following LPS administration, compared to each single treatment. Additionally, the combined drugs significantly decreased TNF-mediated mouse mortality and downregulated TNF-induced MAPK and NF-κB activation. Conclusions: These findings suggest that combined pravastatin and cilostazol is more effective for reducing TNF-driven inflammation through their anti-TNF activity than monotherapy.